Pest treatment composition

ABSTRACT

The present invention provides a pediculicidal and ovicidal composition with an extraordinarily lethal effectiveness that can also be used to remove parasites, such as lice. The pediculicidal and ovicidal composition contains a purified terpene agent such as citronellal, citronellol, citronellyl or a mixture thereof, a short chain alcohol, and a non-aqueous co-solvent and/or surfactant component. The composition more preferably utilizes citronellyl acetate as the active agent. The compositions can be administered topically to humans, animals or any infested areas.

CROSS REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.10/276,647 filed on Nov. 18, 2002, now U.S. Pat. No. 7,282,211, whichclaims priority to PCT Patent Application No. PCT/US01/16367 filed May21, 2001 and U.S. Provisional Application Ser. No. 60/205,843 filed May19, 2000.

FIELD OF THE INVENTION

The present invention relates to agents and methods for the treatment ofpest infestations. In particular, the invention relates to compositionsfor cleansing individuals infested with parasites, such as lice, andtheir ova.

BACKGROUND

Pesticides and insects repellents have long been sought for use againstharmful or annoying parasites. Pests such as lice and fleas areirritating and painful to their human and animal hosts, and can also bevectors for other agents of disease. The pesticides and repellentsavailable in the prior art, however, suffer from various deficiencies.Often, compositions provided as insect repellents are not insecticidal.Furthermore, many compositions are either toxic or generally unpleasantto the host. Still others require too many separate active ingredientsfor efficient production and regulation.

Many synthetic prior art compositions have been proposed as insectrepellents, but have later been determined to be unsuitable for safe useby humans. One common active ingredient in prior commercial compositionsis N,N-Diethyl-m-toluamide (DEET). However, DEET was subsequentlyassociated with causing various undesirable side-effects, such asstinging, damage to mucous membranes, and possibly seizures. In 1989,the Centers for Disease Control issued a cautionary statement regardingthe use of DEET. Many other prior art compounds proposed for use as arepellent have proven unsuitable for topical application to humans orother animals due to their toxic or noxious effect on the infestedindividual.

Various crude oil extracts of certain plants, such as citronella oilobtained from Cymbopogon citrata, or eucalyptus oil obtained fromEucalyptus citriodora, have been provided in the prior art as pestrepellents. However, the oil complex itself is greasy and may have anunpleasant odor, which makes its use undesirable. Furthermore,consistent production of a safe and effective product is difficult, dueto varying amounts of constituent compounds within batches of thesecomplex oils and the difficulty of monitoring a large number ofcomponents. Therefore, insect repellents containing the whole oil ofcitronella, for example, are undesirable due to their limitedrepellency, unpleasant odor and consistency, and unreliable compositionof potentially harmful and unnecessary agents.

Most prior art insect treatments are taught to be effective only withspecific synergistic combinations of multiple pesticides. In the art,there has not been recognized a simple but effective pediculicidal andovicidal composition that is effective and which does not require acombination of excess multiple pesticidal ingredients.

What is needed in the art is an especially effective pediculicidal andovicidal composition. The composition should also be able to cleanse anindividual being treated for infestation.

SUMMARY OF THE INVENTION

The present invention provides a pediculicidal and ovicidal compositioncontaining an active ingredient which demonstrates an extraordinarilylethal effectiveness against parasites, such as lice and their nits. Thepediculicidal and ovicidal composition of the present invention iseffective in cleansing an individual, human or animal, of a pestinfestation.

The composition of the present invention contains an activepediculicidal agent which is at least one purified derivative of anorganic oil. These organic oils are typically comprised of a mixture ofterpenes. An example of an organic oil from which these compounds can bederived is citronella oil. These purified derivatives can be bothpediculicidal and ovicidal. Examples of purified derivatives ofcitronella oil include citronellal, citronellol and citronellyl basedcompounds. Purified nerol and geraniol are found in and can also bederived from citronella oil. Another example of an organic oil fromwhich a terpene compound can be derived is teatree oil. Compounds suchas terpinen-4-ol and cineole are found in and can be derived fromteatree oil. The pediculicidal and ovicidal composition preferablycontains an active agent present in a concentration of about 0.1 to 50%w/w. The pediculicidal and ovicidal composition more preferablycomprises a citronellyl “salt.” The compositions can be administeredtopically to humans, animals or to any infested areas.

The present invention also includes a method of using the pediculicidaland ovicidal compositions. The method includes applying the compositionto the infested area, allowing the composition to remain in contact withthe infested area for a period of time, rinsing the composition from thearea and, in the case of an infestation of hair such as a liceinfestation, combing the infested area with a suitable nit comb.

The method also includes varying the period of time the composition isallowed to remain in contact with the infested area, called theresidence or exposure time, so that lower concentrations of activeingredient can be used while pediculicidal and ovicidal effectiveness ismaintained. For example, the residence time can be increased when acomposition containing a lower concentration of the active ingredient isused in the treatment method.

Therefore, it is an object of the present invention to provide acomposition that is mortally effective against parasites, such as liceand their ova.

It is also an object of the present invention to provide an effectivepediculicidal and ovicidal composition with lower concentrations of theactive ingredient or ingredients that still exhibits pediculicidal andovicidal activity.

Yet another object of the present invention is to provide apediculicidal and ovicidal composition capable of cleansing anindividual infested with a pest, such as lice.

It is further an object to provide a composition that may be used as acleansing shampoo, soap, cream, lotion, gel, spray, mousse or powder.

Another object of the present invention is to provide a method of usinga pediculicidal and ovicidal composition to cleanse an individual of apest infestation.

These and other objects of the invention will be apparent to thoseskilled in the art.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is the log (ln) fit of the dose response data for pediculicidalactivity.

FIG. 2 is the log (ln) fit of the dose response data for ovicidalactivity.

FIG. 3 is the log (ln) fit of the dose response data for undevelopedeggs.

FIG. 4.a. represents the screening model for 100% pediculicidalactivity.

FIG. 4.b. represents the screening model for 100% ovicidal activityprediction profile.

FIG. 4.c. represents the screening model for 100% undeveloped eggs.

FIG. 5 is the log (ln) fit of the prior art dose response data forpediculicidal activity.

FIG. 6 represents the screening model for 100% pediculicidal activity ofthe prior art.

FIG. 7.a. shows the mortality rate of one embodiment of the invention.

FIG. 7.b. shows the mortality rate of one embodiment of the invention.

FIG. 7.c. shows the mortality rate of one embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

A “pest” is meant to include all parasites, such as but not limited toarthropods, arachnids, triatomes, insects, bugs, flies, lice, fleas,mites, gnats, nits, chiggers, mosquitoes, and ticks, for example. Thecomposition of the present invention is, therefore, intended to be usedagainst all parasites which succumb to the lethal properties thereof.

The present invention provides a pediculicidal and ovicidal compositioncomprising or consisting essentially of an active purified terpeneagent, a short chain organic alcohol, and a component selected from anon-aqueous co-solvent or surfactant, or combinations thereof. Thecomposition can also contain an appropriate viscosity modifier.

The present invention provides pediculicidal and ovicidal compositionscomprising an active purified terpene agent. The active agent can be atleast one purified derivative of an organic oil. For example, purifiedderivatives of citronella oil can be used as active agents inpediculicidal and ovicidal compositions. Examples of derivativespurified from citronella oil include citronellal, citronellol andcitronellyl compounds. Other examples include nerol and geraniol.Citronellal, citronellol and citronellyl compounds are currentlyavailable in the trade as food and cosmetic additives. In preferredembodiments, the pesticidal agent utilized is citronellyl. In preferredembodiments, the citronellyl compound is selected from the groupconsisting of citronellyl acetate, citronellyl butyrate, citronellylformate, citronellyl isobutyrate, citronellyl phenylacetate, citronellylproprionate and citronellyl valerate. In a preferred embodiment, thecitronellyl “salt” is the acetate. A highly purified, pharmaceuticalgrade of citronellyl acetate (approximately 97% pure) may be availablefrom Delmar Chemicals (Montreal, Canada). By “purified” herein is meantthat the compound of interest is present in the active agent componentof the composition in a purity or quantity at least 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99% w/w.

The invention preferably provides a pediculicidal and ovicidalcomposition wherein the active purified terpene agent for examplecitronellyl, is in a concentration of between about 0.1% and 50%,preferably between about 1% and 40%, preferably between about 2.5% and30%, preferably between about 5% and 15%, preferably between about 10%and 15% w/w, and preferably about 12.5% w/w.

The compositions also contain a short chain organic alcohol defined asan alcohol having a carbon chain of from 1 to 6 carbon atoms. The shortchain alcohol, such as but not limited to ethanol or isopropanol, isincorporated in a concentration of between about 5% and 99.5%,preferably between about 10% and 30% w/w, preferably between about 15%and 25%, and preferably between about 20% w/w.

The compositions also contain a component selected from the groupconsisting of a non-aqueous co-solvent and a surfactant. The non-aqueoussolvent can be selected from compounds such as but not limited topropylene glycol, butylene glycol, polyethylene glycol, hexylene glycol,methoxypolyethylene glycol, or glycerin. The surfactant can be an ionicsurfactant, such as but not limited to sodium laureth sulfate (availableas STEOL) or sodium lauryl sulfate, or the surfactant can be a non-ionicsurfactant such as but not limited to polyoxyethylene sorbitanmonolaurate, or polysorbate (available as TWEEN or SPAN), orcombinations thereof. This non-aqueous co-solvent and/or surfactantcomponent can be in a concentration of between about 5% and 99.5%,preferably between about 40% and 95%, preferably between about 50% and90%, preferably between about 55% and 80%, preferably between about 60%and 70%, and preferably about 65% w/w.

The compositions also optionally contain a thickening agent to achievean effective viscosity, such as described below, such as but not limitedto hydroxypropyl celluose (non-ionic), and acrylates/C10-30 alkylacrylate crosspolymers (ionic) (available as PEMULIN),polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) (Carbopol™) andcombinations thereof in a concentration of between about 0.01% and 20%w/w, more preferably between about 0.1% and 10% w/w, depending upon thetype of thickening agent. A neutralizing agent such as ortriethanolamine or sodium hydroxide may also be incorporated forthickening of ionic agents.

Some embodiments of the present invention can also include ananti-oxidant/radical scavenging agent such as but not limited toascorbic acid (vitamin C) and its salts, tocopherol (vitamin E), and itsderivatives such as tocopherol sorbate, other esters of tocopherol, andbutylated hydroxy benzoic acids and their salts, such as butylhydroxytoluene, in order to assist in the removal of pests and theirova. A preferred antioxidant/radical scavenging agent is butylhydroxytoluene (BHT). The concentration of the antioxidant/radicalscavenging agent within the present invention is preferably betweenabout 0.01 and 10% w/w, and preferably between about 0.01 and 4% w/w.

The compositions of the present invention can contain other ingredientsso long as the beneficial, pediculicidal and ovicidal nature of theinvention is not adversely affected and so long as the effectiveness ofthe invention is not altered. For example, embodiments of the presentinvention can contain antimicrobial agents such as methylparaben andpropylparaben. Other examples include the addition of a fragrance foraesthetic qualities, addition of propellants for aerosol typeformulations, addition of foaming or conditioning agents. Those skilledin the art realize the vast amount of additional excipients that couldbe added to the formulation for improved aesthetics or delivery of theproduct to the host.

The composition of the present invention can be used in different forms,such as a liquid body soap or a shampoo. In other embodiments, thepresent invention takes the form of a gel, an emulsion, a lotion, anaerosol spray, a mousse, or a cream. Preferably, the composition of thepresent invention is in the form of a surfactant based gel.

The invention also provides a method of treating an individual having aparasite infestation comprising administering to the infestation aninsecticide composition as described above. In particular, thecomposition of the present invention is effective as an insecticideintended for killing and removing lice from humans. Varied treatmentregimens are contemplated as being within the method of treatmentprovided by this invention. Treatment regimens can vary from a singleadministration to repeated administrations over long time periods. Thevarious possible treatment regimens would be apparent to one skilled inthe art based on the invention disclosed herein and are intended to beencompassed in the scope and spirit of the claims.

This method includes applying the composition to the infested area, suchas the hair of an individual with a lice infestation. In the case ofhair, the composition is left on the hair for a period of time referredto as the residence or exposure time. The residence time can vary asneeded to produce effective results. The residence time can be as longas 24 hours and as short as several seconds. Preferably, for thetreatment of lice, the residence time is between 1 and 30 minutes. Morepreferably, the residence time is between approximately 5 and 20minutes. At the end of the residence time, the composition is rinsedfrom the area of infestation. These treatment steps of applying andrinsing can be repeated one or more times to complete the removal of thepest infestation. The time period between uses of the pest removingcomposition can vary as needed to remove the pest infestation from theindividual.

Before or after application of the composition the hair may be combedwith a suitable nit comb, however combing is not necessarily required.Any suitable nit comb can be used in the described method of use of thecomposition of the present invention. A suitable nit comb may be made ofvarious materials such as metal and plastic. Metal teeth are sturdierand stiffer than those composed of materials such as plastic. Nit combswith metal teeth therefore often last longer than nit combs withoutmetal teeth. The number of teeth and the diameters of the teeth can alsovary. The spacing between teeth can also vary; however, the teeth shouldbe close enough to one another to remove nits. The distance betweenteeth should be 0.3 mm or less, the generally accepted width of nitsattached to human hair. Preferably, a nit comb such as the ALB006 isused, which is available from Albyn Stonehaven Ltd. (Stonehaven,Scotland). This comb has 62 metal pins arranged side by side which actas the teeth of the comb. These pins extend approximately 12.5 mm from aplastic piece which acts as the handle of the nit comb. The pins oneither end have a diameter of 0.9 mm and the 60 inner teeth have adiameter of 0.6 mm. The gap between the teeth is 0.3 mm.

To the inventors' knowledge, there has not previously been a recognitionof the pediculicidal and ovicidal effectiveness of the presentcompositions containing active purified terpene agents such ascitronellyl, citronellal, citronellol, nerol or geranol that possess asurprising degree of pediculicidal and ovicidal effectiveness incombination with the short-chain alcohol, other non-aqueous co-solventsand/or surfactants and optionally an appropriate viscosity modifier. Itis surprising that other detergents, such as aqueous detergents, oracids, such as acetic acid (in concentrations of greater than 5%), arenot required in the invention. It is noted that propylene carbonate isnot a necessary ingredient to provide the observed synergistic effect ofthe invention. Additionally, to the inventors' knowledge, there has notbeen a previous recognition or demonstration of the effectiveness of thepresent invention at cleansing individuals of pest infestations. Oneskilled in the art can routinely modify the relative concentrations ofthese components, and accordingly the ratio of their combination, toyield a functional pesticide composition.

Without being limited by theory, it is believed that the composition ofthe present invention is surprisingly effective due in part to thepurification of individual compounds. Citronella oil is a complexmixture containing components which may ordinarily mask the potentialeffectiveness of the individual purified terpene pesticidal agents, suchas citronellyl, citronellol, and citronellal, as disclosed by thepresent invention. It also appears that a synergistically beneficialeffect is achieved in the compositions of the present invention.

The present invention is intended to be administered topically toinfested areas of an individual, such as the hair and scalp or pubicareas. The composition is preferably provided in the form of a liquid orsolid, such as shampoo, soap, cream, or lotion. The inventioncontemplates that various other complimentary ingredients can beincluded, such as an antipruritic agent, a pH modifier, or as a generalmedium. For example, glycerins, glycols, alcohols, lanolins, aloe veragel, may be provided in the composition. The preferred compositions areshampoos and soaps containing ingredients capable of assisting incleansing individuals of the debris of dead parasites.

The composition may also be provided in sun screening, tanning or anyother topically applicable products. Other uses of the composition arecontemplated, such as a pediculicidal and ovicidal spray or logger forapplication directly to pests or potentially infested areas. Forexample, the composition can be provided as a pesticide and cleaningagent for fruits and vegetables. The composition can additionally serveas a parasite repellent for humans, cats, dogs, birds, cattle, or sheep,for example. The composition may also be used as a carpet powder, or asa detergent additive, rinse or spray for clothing, bedding or otherfabrics. The composition may also be used as an aerosol bomb or as aroom spray. Other such uses would be apparent to one skilled in the artupon contemplating the invention disclosed herein and such uses areintended to be encompassed in the scope and spirit of the claims.

EXAMPLES Summary of New In Vitro Assessments Developed

Currently, the most widely used in vitro methods used to assess theinsecticidal qualities of a lice treatment product or compound are ASTMmethods E 938-83, “Standard Test Method for Effectiveness of Liquid,Gel, or Cream Insecticides Against Adult Human Lice,” and E 1517-93,“Standard Test Method for Determining the Effectiveness of a Liquid,Gel, Cream, or Shampoo Insecticides Against Human Louse Ova.”

For these methods, a strain of human body lice has been adapted to feedon rabbit blood. The current ASTM tests are used early in thedevelopment process for initial pre-clinical assessments of possiblelice treatments. Also, these tests are sometimes used to “substantiate”marketing claims of pediculicidal and/or ovicidal activity. Poorcorrelation between the in vitro results and in vivo efficacy may beseen especially for ovicidal assessments.

Therefore, a need existed to develop new in vitro methods thatincorporate different application and assessment techniques.Incorporation of the new techniques hopefully would result in a bettercorrelation between the methods for adequate prediction of in vivoactivity and future product success.

Two main critical differences exist between the in vitro and in vivomethods that could lead to the limitations. First, the in vitro testincorporates human body lice that have been adapted to feed on rabbitblood not human head lice, which feed on human blood. It is plausiblethat a difference in efficacy could be observed based on the differencein species being tested. Second, in the in vitro tests, lice or nitsbeing treated are completely submerged in the test solution for theentire identified residence time. This method of “application” of theproduct is drastically different than topical application in vivo. Asimilar in vivo application would be to submerge a child's hair in thetest product. This is obviously not the most practical or safe method ofactual application.

This “first scenario” (difference in species) was initiallyinvestigated. The ASTM ovicidal assessment test was duplicated in thefield using human head lice nits attached to hair. The hair was clippedwith the attached nit and treated identically according to the ASTMmethod. No statistically significant difference in efficacy wasobserved. This indicates that good correlation exists between using theadapted strain of human body lice ova versus actual human head lice ova.Therefore, efforts were focused onto the application and assessmenttechniques.

Since submersion would never be a justified application technique invivo, the application aspect of the pediculicidal assessment wasamended. Instead of submerging the lice in the product for the entireresidence time, the lice were allow to crawl on a small piece of gauzeand then submerge in the test product for 5 seconds. They were thenremoved and placed in an empty petri dish where they remainedundisturbed for the remainder of the identified residence time.Obviously, this application procedure is much more indicative of in vivoapplication where the product is applied from the bottle in a largequantity, worked into the hair (thinning effect), and allowed to sit forthe identified time.

Assessment of the new application technique was performed with thecritical strength of citronellyl acetate (in original vehicle)previously identified using the original ASTM method. The originalmethod showed that when 5.0, 7.5, 10.0, and 12.5% citronellyl acetatewere tested that 5.0% was the critical strength as it was the onlystrength not to exhibit 100% activity (actually was 91.9%). When testedwith the new application technique, the 5.0% strength possessed only62.3%. This indicates that the new method with the different applicationtechnique is much more rigorous or may help to explain the lack of 100%in vivo efficacy.

The application technique for the in vitro ovicidal test method was alsoamended. In the ASTM method, adult lice were allowed to lay eggs onclipped human hair. Then, ten hair strands, 1 nit attached to each, weretaped to an applicator stick. Finally, the applicator stick with hairand nits was submerged in the test solution for the entire identifiedresidence time. The new application method incorporated “tresses” ofhair. Each tress was a collection of human hair bundled at one end, andthe lice were allowed to lay numerous eggs on these tresses (about200-300 nits per tress). The tresses were woven into sections of a humanhair wig, and the wig was secured to a non-porous solid surface “head.”The test product and a control (water) was applied each section of thewig with a method similar to typical shampooing or applying a creamrinse in under 2 minutes. After application, the product was allowed toremain, undisturbed, in contact for the identified residence time. Afterthe residence time, the wig was rinsed thoroughly (until no visiblesigns of product remained) with tap water and towel dried. The tresses,with nits, were removed from the wig and incubated under appropriateconditions for 14 days post treatment.

In addition to the new application technique, new assessments were alsoincluded in the new in vitro ovicidal study. These new assessments wereincorporated in an effort to determine the level of the productspenetration through the various protective structures of the nit. Intheory, these additional assessments would provide much betterevaluation of a product's ability to penetrate and potential in vivoovicidal activity. The two new assessments were determination of levelof hatching (ie: “half-hatched”) and “eye spot formation”

Level of hatching is basically a “pass/fail” assessment of penetration.For example, if the product penetrates the nit pore but not the nitmembrane (used for regulation of gas transport), the product willcollect around the membrane (common with currently marketed products).Therefore, the nit will actually develop and begin to hatch. However,once the nymph has broken the membrane, it is exposed to a certain levelof active. If enough active is present, it will kill the nymph whilehatching, and this can be documented as a “half hatched” nit. If the nitis exposed but not killed, it could become resistant to future treatmentwith the compound. This could be one explanation of the documentedresistance of human head lice to current actives.

Assessment and location of eye spot formation provides a more detailedmeasurement of penetration. At the time of treatment, the nits have notdeveloped eyespots. Therefore, if the product completely penetratesinside the nit, it will be killed at the time of exposure and nodevelopment will occur. However, if eyespot formation is seen itindicates lack of penetration, and the location of the eyespot can evenpredict the level of penetration.

Finally, the two additional assessments were used to tabulate “%Undeveloped” nits. Nits that showed no signs of development (i.e.excludes nits that were half hatched or had eye spot formation) weretabulated. The number of undeveloped nits was divided by the totalnumber of nits treated and multiplied by 100 for reporting “%Undeveloped.”

A vehicle with 10.0% and 12.5% strengths of citronellyl acetate was usedto assess the ovicidal activity with the new method. The ASTM methodresulted in 100% activity for both strengths. While the new methodresulted in 96.2% and 98.1% activity respectively, only 53.4% and 72.0%of the nits were undeveloped respectively. Obviously, the new methodshows that while the overall effect may be positive (i.e. almost 100%)the underlying ability of the product to penetrate may not correlatewith the activity. This study was carried out in a controlled manner andstill resulted in nit development. This can easily explain the lack ofovicidal activity in less controlled in vivo studies.

As the new methods clearly are better tools for assessment, they wereused for all future in vitro formulation assessments.

Summary of Formulations Developed and Hypotheses Involved

Previous development work of a lice treatment product incorporatingcitronellyl acetate as an active ingredient resulted in a product thatconsisted of two separate components. The components had to be mixedjust prior to use due to a lack of product stability upon mixing. Thistwo-component product could result in improper use or mixing (humanerror), more potential for side effects, less patient compliance, andless willingness to use the product. Also, the formulation incorporatedacetic acid and proved to cause considerable dermal irritation (PDItesting of the two-component formulation after mixing resulted in ascore of 6.75, a severe irritant).

Therefore, a considerable amount of research was initiated to develop aproduct that would be less irritating, even more active, and could bepackaged in a single container. First attempts to overcome these issuesresulted in an “anhydrous” formulation. The formulation was anoil-in-water (O/W) emulsion (instead of a solution, originaltwo-component formulation) and is referenced in U.S. Pat. No. 5,902,595.The product was designed as a cream rinse incorporating conditioners inlieu of the surfactant, sodium laureth sulfate. For irritation issues,it was believed that the conditioner might soothe the irritatingeffects. For stability issues, it was hypothesized that by emulsifyingthe citronellyl acetate (an oil), it would be protected from the aciddegradation process and oxidation resulting in a significant increase instability for the single component formulation. Following is a summaryof that formulation:

Ingredient % (w/w) IPA 20.0 Acetic Acid 5.0 Cedepal HC 15.0 PropyleneGlycol 20.0 Glycerin Diluent Methylparaben 0.2 Propylparaben 0.1Citronellyl Acetate 12.5

However, in vitro testing revealed that while this formulation waspediculicidal (99.8%) it possessed no ovicidal activity (1.6%). Due tothe lack of in vitro ovicidal efficacy, additional emulsifiedformulations were developed in attempt to incorporate the sodium laurethsulfate and acetic acid into a single component. The theory was that inan O/W emulsion, citronellyl acetate (an oil) would be protected fromthe acetic acid (soluble in the water phase). The protection from aciddegradation would result in increased stability. Many O/W formulationswere developed consisting of various types of emulsifiers.

In addition, efforts were focused on increasing viscosity according tothe hypothesis that increasing the viscosity of the formulations wouldincrease stability (increasing viscosity will slow down collisions) andefficacy (increase contact time with pest). Theoretically, increasingthe viscosity of the formulation will impede molecular motion and slowdown particle collisions, directly affecting the degradation kineticsand slowing the decomposition of the active ingredient. Also, increasingviscosity would increase the contact time and decrease evaporation ofthe active ingredient while on the pest. This would result in the pestbeing exposed to more active ingredient for longer durations of time,directly increasing efficacy.

Various different O/W formulations were developed in attempt to increasethe viscosity of the overall product. Most of these formulationsincorporated the same ingredients as the original formulation(citronellyl acetate, IPA, acetic acid, methylparaben, andpropylparaben). However, for formulation of a thicker emulsion, mineraloil and thickening, emulsifying agents were substituted in lieu of asurfactant. Examples of thickening, emulsifying agents incorporated intothe formulation are various grades of Carbopol™ (carbomer), PVP(polyvinylpyrrolidone), Pemulen® (Acrylates/C10-30 Alkyl AcrylateCrosspoly-mer), Klucel HF® (hyroxypropyl cellulose), hydroxyethtylcellulose, hydroxypropylmethyl cellulose, and each was used individuallyand in combination with the others. Also, buffer systems (such as sodiumacetate trihydrate) and neutralizing agents (such as TEA,triethanolamine) were included as needed. Following is a tablesummarizing the ingredients and ranges used in the most desired O/Wemulsions developed.

Ingredient % (w/w) IPA 20.0 Acetic Acid  5.0 Purified water 59.1-60.8Pemulen ® TR-1 1.75-3.50 Citronellyl Acetate 10.0 Methylparaben 0.0-0.2Propylparaben 0.0-0.1 Mineral Oil  2.0

One specific formulation (included in above ranges with 1.75% Pemulen®TR-1) was tested for stability and in vitro pediculicidal efficacy. Thisformulation resulted in much greater stability as a single component butin vitro pediculicidal testing indicated poor efficacy.

Because a lack of efficacy existed while still incorporating aceticacid, focus was shifted on developing a single component, acid free,clear gel formulation. Clear gel formulations offer many positiveattributes. First, they are typically thickened alcoholic solutions.This allows for greater drug uniformity, greater drug loading, greatercontact time, and less phase separation. Also, topical gels canincorporate non-aqueous solvents such as glycerin and propylene glycolthat also can enhance penetration and possess humectant qualities, whichcan increase the penetration of the active and help to overcome anyirritating effects of other ingredients.

These new formulations incorporated an antiparasitic compound,citronellyl acetate, as the active purified terpene agent, butcitronellol, citronellal, gerianol, and/or nerol can also be used, forexample. A short chain organic alcohol was included as a solvent and wasused as the diluent. Specific examples of alcohol used are isopropylalcohol and ethanol. Other non-aqueous solvents were included such aspropylene glycol and glycerin. Other anhydrous glycols such as butyleneglycol, hexylene glycol, polyethylene glycol, methoxypolyethyleneglycol, and their derivatives could be included. Also to stabilize theformulation, an antioxidant/radical scavenging agent, butylhydroxytoluene (BHT), was incorporated. Also, chelating agents can beadded to improve stability since they form complexes with metal ionsrendering them unavailable for reaction and/or as a catalyst for otherreactions, which usually results in increased stability of theformulation. An example of a possible chelator is EDTA. Antimicrobialpreservatives, methylparaben and propylparaben, were included and arecommonly used for inhibition of microbial growth in liquid or semi-solidformulations. Other examples of common preservatives are benzoic acid,sodium benzoate, and benzalkonium chloride (BAK).

Some of the new formulations were thickened with alcohol compatiblepolymers such as hydroxypropyl cellulose (HPC, “Klucel® HF),polyvinylpyrrolidone (PVP), and Pemulen TR-1® and TR-2® (CTFA name:Acrylates/C10-30 Alkyl Acrylate Crosspolymer), hydroxyethyl cellulose,and hydroxymethylpropyl cellulose. Various amounts of the thickenerswere added to optimize the viscosity of the formulation. In theory, thiswould increase the contact time of the active ingredient with the pestand decrease side effects such as burning of the eyes and mucousmembranes (due to a thin product running off the hair and onto the faceand eyes).

The following two tables summarize some of the single component, acidfree, o/w emulsion and clear gel formulations developed and variousmethods used to manufacture the product:

Ingredient Ranges developed (% w/w) IPA  0.0-58.45 Ethanol (95%) 0.0-51.95 BHT 0.05 Propylene Glycol 10.0-20.0 Glycerin 10.0-20.0 KlucelHF ® (HPC) 0.0-2.0 Pemulen TR1 0.0-3.0 Citronellyl Acetate 0.5-8.0

Ingredient % (w/w) Citronellyl acetate 8.0, 10.0, 12.5 Methylparaben0.0, 0.2 Propylparaben 0.0, 0.1 PVP 0.0, 1.0 Pemulen ® 0.25-2.5  GlacialAcetic Acid 0.0, 5.0 IPA 20.00 Sodium Laureth Sulfate (25%)  0.0, 50.0TEA 0.0, 0.4 Sodium Hydroxide 0.0-1.0 Purified Water diluent

Preparation of Thickened Existing Acetic Acid Formulations withoutNeutralizer

Step Description 1 Add alcohol to an adequately sized mixing vessel (#1)and begin mixing 2 While mixing, add methylparaben and propylparaben andmix until completely dissolved 3 While mixing, add citronellyl acetate,then Steol CS-230, then purified water mixing for 2 minutes after eachaddition 4 Heat the solution from step #3 to 40-45° C. 5 Add Pemulen tothe hot solution from step #4 and mix well while maintaining thetemperature at 40-45° C. until completely hydrated 6 Cool to roomtemperature (about 25° C.)

First Preparation of o/w Emulsion Formulations without Neutralizer

Step Description 1 Add citronellyl acetate and mineral oil to anadequately sized mixing vessel (#1), begin mixing, and heat to 60-65° C.2 While mixing and maintaining the temperature at 60-65° C., add Pemulenand mix until well dispersed 3 In a separate, adequately sized vessel(#2), mix water and alcohol and heat to 50-55° C. 4 While mixing andmaintaining the temperature at 50-55° C., disperse the PVP in thesolution from step #3 (in vessel #2) and continue mixing until the PVPis well hydrated 5 Add glacial acetic acid to the hot solution from step#4 (vessel #2) and mix well while maintaining the temperature at 50-55°C. 6 While mixing and maintaining the temperature at 50-55° C., add thesolution in vessel #1 to that in vessel #2 and mix until completelyuniform 7 Cool to room temperature (about 25° C.)

Second Preparation of o/w Emulsion Formulations without Neutralizer

Step Description 1 Add water, alcohol, and acetic acid to an adequatelysized mixing vessel (#1), begin mixing, and heat to 40-50° C. 2 Whilemixing and maintaining the temperature at 60-65° C., add methylparabenand propylparaben and mix until completely dissolved 3 While mixing andmaintaining the temperature at 40-50° C., disperse the PVP in thesolution from step #2 (in vessel #1) and continue mixing until the PVPis well hydrated 4 Add citronellyl acetate and mineral oil to aseparate, adequately sized mixing vessel (#2), begin mixing, and heat to60-65° C. 5 Add Pemulen to the hot solution from step #4 (vessel #2) andmix well while maintaining the temperature at 40-50° C. until completelyhydrated 6 While mixing and maintaining the temperature at 50-55° C.,add the solution in vessel #1 to that in vessel #2 and mix untilcompletely uniform 7 Cool to room temperature (about 25° C.)

Third Preparation of o/w Emulsion Formulations without Neutralizer

Step Description 1 Add water, alcohol, and acetic acid to an adequatelysized mixing vessel (#1) and mix for 2 minutes 2 While mixing, addmethylparaben and propylparaben, begin heating the solution to 40-50°C., and mix until completely dissolved 3 While mixing and maintainingthe temperature at 40-50° C., disperse the PVP in the solution from step#2 and continue mixing until the PVP is well hydrated 4 In a separate,adequately sized mixing vessel (#2), add citronellyl acetate and mineraloil, begin mixing, and heat to 35-45° C. 5 While mixing and maintainingtemperature at 40-50° C., add the contents of vessel #2 to that invessel #1 6 Add Pemulen to the hot solution from step #5 and mix wellwhile maintaining the temperature at 40-50° C. until completely hydrated7 Cool to room temperature (about 25° C.)

Preparation of o/w Emulsion Formulations with Neutralizer

Step Description 1 Add citronellyl acetate and mineral oil to anadequately sized mixing vessel (#1), begin mixing, and heat to 60-65° C.2 While mixing and maintaining the temperature at 60-65° C., add Pemulenand mix until well dispersed 3 In a separate, adequately sized vessel(#2), mix water and alcohol, and heat to 50-55° C. 4 While mixing andmaintaining the temperature at 50-55° C., disperse the PVP in thesolution from step #3 (in vessel #2), and continue mixing until the PVPis well hydrated 5 Add neutralizer (TEA or NaOH) to the hot solutionfrom step #4 (vessel #2) and mix well 6 While mixing and maintaining thetemperature at 50-55° C., add the solution in vessel #1 to that invessel #2, and mix until completely uniform 7 Cool to room temperature(about 25° C.)

Preparation of Clear Gel Formula

Step Description 1 Add alcohol to an adequately sized mixing vessel (#1)and begin mixing 2 While mixing, add BHT and mix until completelydissolved 3 While mixing, add propylene carbonate, then propyleneglycol, and then glycerin mixing for 2 minutes after each addition 4While mixing, slowly add Klucel (or other type of thickener) and mixuntil completely hydrated and a uniform gel is achieved

Five specific formulations were developed that possessed the bestaesthetic qualities and could be tested for the effect of the alcoholselection and viscosity. In general two thin (water like) formulationswere made, 1 with ethanol and the other with IPA. The third formulationincorporated ethanol and Klucel® HF as a thickener (resulted in molassestype consistency). Each was tested for in vitro efficacy. Following arethe three formulations and in vitro test results:

Formulation 022800-006A:

Ingredient % w/w IPA 51.95 BHT 0.05 Propylene Glycol 20.0 Glycerin 20.0Citronellyl Acetate 8.0Formulation 022800-007A:

Ingredient Ranges developed (% w/w) Ethanol (95%) 51.95 BHT 0.05Propylene Glycol 20.0 Glycerin 20.0 Citronellyl Acetate 8.0Formulation 022800-007B:

Ingredient Ranges developed (% w/w) Ethanol (95%) 50.95 BHT 0.05 KlucelHF ® 1.0 Propylene Glycol 20.0 Glycerin 20.0 Citronellyl Acetate 8.0In Vitro Data

% Pediculicidal % Ovicidal % Formulation Activity Activity Undeveloped006A 80.3 99.2 98.1 007A 41.7 Not Tested Not Tested 007B 88.9 100 99.5

The testing shows a twofold increase in pediculicidal effectiveness whenIPA is used instead of ethanol (006A vs. 007A). Also, a twofold increasein effectiveness is seen when the thin ethanol formulation is thickened(007A vs. 00713). However, both the thin IPA formulation and thethickened ethanol formulation are ovicidal and result in basically nodevelopment of the nit after exposure. Surprisingly, acetic acid was notrequired to achieve successful ovicidal activity. Inclusion of propylenecarbonate had absolutely no effect on the efficacy of the formulations.The in vitro data indicates that an optimized formulation wouldincorporate IPA as the alcohol, should be thickened, and would not needto incorporate propylene carbonate.

Therefore, additional formulations were developed and tested. The firstadditional formulations were hybrids of 006A and 007B incorporating IPAas the alcohol and Klucel® HF for thickening. A series of the vehiclewere made with decreasing amounts of citronellyl acetate. Also, in otherformulations, Pemulen TR-1® was incorporated in lieu of Klucel® HF toassess the effect of thickener used. These formulations were tested forin vitro efficacy, and following is a summary of the formulations and invitro pediculicidal activity:

Ingredient 041100-002A 041100-003A 041100-004A 041100-004B 041800-005A041800-006A 041800-007A IPA 53.95% 56.45% 57.95% 58.45% 53.45% 48.95%49.95% BHT 0.05% 0.05% 0.05% 0.05% 0.05% 0.05% 0.05% Propylene Glycol20.00% 20.00% 20.00% 20.00% 19.70% 20.00% 20.00% Glycerin 20.00% 20.00%20.00% 20.00% 19.80% 20.00% 20.00% Propylene Carbonate Klucel HF ® (HPC)1.00% 1.00% 1.00% 1.00% Pemulen ® TR1 2.00% 3.00% 2.00% CitronellylAcetate 5.00% 2.50% 1.00% 0.50% 5.00% 8.00% 8.00% % Pediculicidal 79.793.1 42.9 67.2 74.6 100 100 Activity

The data indicates that neither the type of thickener nor minorviscosity differences affect the efficacy as long as the final productis produced from a solution that is thickened to form a clear gel.

While fairly high levels of Pemulen® were required to reach the desiredconsistency, it should be noted that the amount of Pemulen TR-1® andTR-2® required for thickening the formulation could be greatly reducedby adding a small amount of a neutralizing agent. These neutralizerscould be any strong or weak bases, and specific examples are sodiumhydroxide, triethanolamine (TEA), and aminomethyl propanol. If theconcentration of alcohol is greater than 50%, a more alcohol solubleamine may be required. Specific examples are Quadrol® or Neutrol®(tetra-2-hydroxypropyl ethylene diamine), Ethomeen® C-25 (PEG 15Cocamine), DPA (diisopropylamine), or AMP (amino methyl propanol).Following is an example of one formulation developed that incorporatedless thickener and a neutralizer:

Ingredient 113000-044A IPA 15.0% BHT 0.05% Propylene Glycol 75.06%Citronellyl Acetate 10.00% Pemulen ® TR1 0.85% Sodium Hydroxide 0.04%

A series of formulations were prepared with various concentrations ofIPA and were tested for in vitro pediculicidal and ovicidal efficacy(wig method). All of the formulations incorporated 8.0% citronellylacetate and were identical with the exception of alcohol concentration.Due to the minimization efforts, propylene glycol was used as thediluent instead of the alcohol. Following is a summary of theformulations prepared and their corresponding activities:

Ingredient % (w/w) IPA 10.00 20.00 30.00 40.00 Control BHT 0.05 0.050.05 0.05 — Propylene glycol 59.95 49.95 39.95 29.95 — Glycerin 20.0020.00 20.00 20.00 — Pemulen ® TR1 2.00 2.00 2.00 2.00 — Citronellylacetate 8.00 8.00 8.00 8.00 — % Ped. Act. 100.0 100.0 100.0 100.0 12.0 %Ovicidal Act. 100.0 100.0 100.0 99.5 10.2 % Undeveloped Eggs 99.5 99.898.0 98.0 53

As evident from the study, activity was not related to the IPAconcentration.

A series of formulations were also prepared for an in vitro doseresponse study. The dose response study was designed by formulating theclear gel vehicle with 10% IPA and various levels of citronellyl acetatebetween 0.0 to 10.0%. The formulations were assessed for in vitropediculicidal activity using the modified methods previously described.All formulations possessed viscosities between 1500-3000 cps, andfollowing is a summary of the clear gel formulations that were preparedfor the dose response study and the resulting data from the assessments:

Ingredient % (w/w) IPA 10.00 10.00 10.00 10.00 10.00 10.00 10.00 BHT0.05 0.05 0.05 0.05 0.05 0.05 0.05 Propylene 67.95 66.95 65.45 62.9561.45 59.95 57.95 glycol Glycerin 20.00 20.00 20.00 20.00 20.00 20.0020.00 Pemulen ® 2.00 2.00 2.00 2.00 2.00 2.00 2.00 TR1 Citronellyl 0.001.00 2.50 5.00 6.50 8.00 10.00 acetate % Killed 14.9 5.1 28.7 25.0 81.297.9 99.0 % Corrected 21.3 6.7 54.2 59.7 89.4 100 100 Ped. Act. %Undev'd 16.4 21.3 12.0 98.3 74.2 85.9 65.5 Eggs Corrected % 1.1 37.737.8 100 84.2 98.5 97.9 Ovicidal Act.

An ANOVA analysis was performed (with α=0.025) to determinestatistically significant activity above that of the water control(p-values>α indicate no significant activity). Following were theresults of the analysis:

Data Analyzed % Ped. Act. % Ovicidal Act. % Undev'd Eggs Strengthp-value p-value p-value Vehicle 0.324999 0.992901 0.228258 1.0% 0.7595470.045519 0.038553 2.5% 0.03279 0.004057 0.259956 5.0% 1.5 × 10⁻⁶ 4.8 ×10⁻⁵ 1.2 × 10⁻⁵ 6.5% 4.2 × 10⁻⁶ 0.001045 0.001009 8.0% 4.2 × 10⁻⁶ 4.8 ×10⁻⁵ 0.000412 10.0%  2.1 × 10⁻¹⁰ 6.1 × 10⁻⁵ 0.000118

The ANOVA analysis identified that products incorporating greater than2.5% citronellyl acetate are capable of statistically significantpediculicidal activity and a statistically significant number of eggsremaining undeveloped. It also identified that products incorporatinggreater than 1.0% were capable of statistically significant ovicidalactivity.

The resulting data for pediculicidal activity (FIG. 1), ovicidalactivity (FIG. 2), and for undeveloped eggs (FIG. 3) was statisticallymodeled using a log (ln) fit of the data typical of that observed withdose response data. In addition, a screening model was used to identifythe minimum dose predicted to elucidate 100% pediculicidal activity invitro (FIG. 4.a.), 100% ovicidal activity in vitro (FIG. 4.b.), and 100%undeveloped eggs in vitro (FIG. 4.c.).

For comparison purposes as shown in FIGS. 5-6, the same techniques wereapplied, retrospectively, to the preferred formulation identified inprevious art incorporating a thin add-mix system with acetic acid (U.S.Pat. No. 5,902,595) in order to predict the active required for 100% invitro pediculicidal activity.

Calculations were performed with the resulting data to transform thepredicted In result into citronellyl acetate concentration by fittingthe result (x) into the simple following inverse natural log equation:e^(x)=% citronellyl acetate

Required citronellyl acetate concentrations were calculated from thepredicted values of the prior art and gel formulations. Interestinglyfor the prior art formulation, no dose could be predicted to yield 100%activity as the response maximum was 85% activity at 18.4% citronellylacetate.

Surprisingly, however, when the corresponding results for the clear gelformulation of 2.27, 2.19, and 2.74 from the screening model therespective corresponding calculated values were 9.67% citronellylacetate required for 100% pediculicidal activity, 8.93% for 100%ovicidal activity, and 15.5% required for 100% undeveloped eggs.Interestingly, this specific embodiment of the invention exhibited morelethal qualities with less than half the amount of citronellyl acetate.

Three optimized clear gel formulations were prepared in attempt toidentify the most preferred embodiment of the invention. All threeformulations incorporated either 10.0% or 12.5% citronellyl acetate andeither 15% or 20% IPA. Two formulations used propylene glycol as thebase, and both were thickened utilizing Pemulen® and a neutralizationstep with sodium hydroxide. The third formulation substituted SteolCS-230 (sodium laureth sulfate) for the entire amounts of propyleneglycol and glycerin and was thickened through higher levels of Pemulen®.This third formulation also did not incorporate the BHT due to immediateavailability issues. Following are the three formulations prepared:

Formulation # % (w/w) Ingredient 1 2 3 IPA 15.00 15.00 20.00 BHT 0.050.05 0.00 Propylene glycol 75.06 72.56 0.00 Steol CS-230 0.00 0.00 65.50Pemulen ® TR1 0.85 0.85 2.00 Citronellyl acetate 10.00 12.50 12.50Sodium Hydroxide 0.04 0.04 0.00 Result Viscosity 5,750 cps 4,300 cps1,450 cps

An additional new in vitro pediculicidal activity assessment wasimplemented in attempt to elucidate preferred embodiments and ultimateconfirmation of potential efficacy and assessment of the threeformulations. The new method mimicked the ASTM method except that humanhead lice were collected and used for the evaluation. For theassessment, lice were collected from patients that had recentlyexperienced multiple product failures. This assured a sampling of licesuspected to possess resistance to current treatments. The lice werecollected on nylon gauze patches inside of a petri dish. The lice werethen used for experimentation within 30 minutes after collection. Thelice were separated into groups of 10 and then treated.

The lice were submerged for 1 minute and removed but not rinsed for theremainder of the exposure period (10 minutes for all assessments). Thelice were rinsed thoroughly with tap water, blotted dry, and placed on anew, dry piece of nylon gauze. The lice were observed for signs of lifeunder a stereomicroscope at various time intervals up to 3 hours afterexposure. Lice were classified as “appeared dead” if no physicalmovement existed or “alive” if the lice were crawling or otherwisephysically moving. Percentages were calculated as shown in FIGS.7.a.-7.c. for each classification at each time interval.

Surprisingly for formulations #1 and #2, initial observation timesindicate a high level of apparent kill, but as time elapsed the licerecovered and lived. Therefore, while these treatments may show efficacyto non-resistant lice, they most likely will not display any efficacy tothe resistant ones. However, Formulation #3 (with sodium laurethsulfate, Steol CS-230) apparently overcame the resistance mechanism andresulted in 100% kill. This indicates that the product will most likelybe effective against resistant lice in the field. Obviously, the studyresults identified the surfactant based, clear gel product as thepreferred embodiment.

Following is a summary of the preferred gel embodiments, and the mostpreferred, single embodiment of the invention and the method ofproducing the product:

Ingredient % Most preferred IPA 5.0-30.0% 20 BHT 0.00-0.05   0.00 SteolCS-230 52.45-88.5% (qs) 65.5 (qs) Pemulen ® TR1 1.5-2.5%  2.0Citronellyl acetate 5.0-15.00  12.50

Step Description 1 Add alcohol to an adequately sized mixing vessel andbegin mixing 2 While mixing add BHT and mix until completely dissolved 3While mixing, add citronellyl acetate and mix for 2 minutes 4 Whilemixing, add sodium laureth sulfate (Steol CS-230) and mix for 2 minutes5 While mixing, slowly add Pemulen to the vortex and mix until wellhydrated and uniformly thickened

This optimized surfactant based formulation was duplicated and used forcomparative pre-clinical toxicology assessments. These assessments wereperformed and results classified identically to those for prior art(add-mix system, U.S. Pat. No. 5,902,595) for a direct comparison ofskin irritation. For the skin irritation testing, an additional exposuretime was assessed for the preferred embodiment. Therefore, the studyassessed irritation associated with both a 1 and 4-hour exposure to thetest product. The Primary Irritation Index (PII) was calculated at 1 and4-hour exposures. The resulting PIIs were 3.58 for the 1-hour exposureand 4.54 for the 4-hour exposure, both of which classify as a “moderateirritant.” Again surprisingly, the preferred embodiment resulted indrastically improved dermal irritation profiles as compared to the priorart that resulted in a PII of 6.75 indicating that the product was“severely irritating”.

A variation of the preferred embodiment was prepared with one of thechirally pure terpenes, R- or S-citronellol. The formulations wereprepared and tested for in vitro pediculicidal activity using lab liceand the 5 second immersion technique. Interestingly, both formulationsresulted in 100% activity. However, a significant difference in thesymptoms of exposure and manner of death was observed between the twogroups of lice. Immediately after rinsing, there was no differencebetween the groups. In both cases 3 to 4 lice were beginning to showmovement, and some others were inactive but showed gut movement. After60 minutes, physical signs of exposure began to differentiate. The liceexposed to S-citronellol were basically walking as normal, but 10 licewere showing tonic-clonic spasms similar to that seen for lice exposedto permethrin or other pyrethroids. Only 1 of the lice exposed toR-citronellol appeared alive and normal, 4 others were trying to walkbut the rest were completely immobilized. After 180 minutes, 4 four liceexposed to R-citronellol were lying down with “waggling” limbs and therest remained completely immobilized. For the ones treated withS-citronellol, 2 were lying down with “waggling” limbs, 1 louse walkinguncomfortably with stiff limbs, and the remainder were immobile. Whileboth pure enantiomers eventually exhibited 100% pediculicidal activity,the symptoms and physical characteristics after exposure varieddrastically.

Scanning electron microscopy was also used to assess possibledestruction of the cuticle of lice upon treatment with the preferredembodiment. Lice and eggs were collected before and after exposure tothe gel formulation (with racemic citronellyl acetate), analyzed withSEM, and the images were compared to discern cuticle destruction. Theimaging clearly revealed cuticle dissolution and surface “erosion.”Specifically images showed the most drastic effects around the dorsalcolumn (principal point of thoracic muscular attachment, mainly themuscles that operate the legs) for the treated louse than the untreated.However, images of leg joints show very little or no effects on thetissues of the joints. Comparative images of eggs also revealed evidenceof surface destruction. Imaging also revealed a significant differencein opercular pore separation, definition, and height.

The Examples above are intended to be demonstrative, but not exhaustive,of the embodiments contemplated by the present invention. It is intendedthat other deviations apparent to those skilled in the art from theinvention described above are encompassed in the scope and spirit of theinvention.

1. A pediculicidal and ovicidal composition consisting essentially ofcitronellyl acetate in a concentration of about 2.5%-15% w/w of thetotal composition, a viscosity modifier selected from the groupconsisting of hydroxypropyl cellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxyethyl cellulose (HEC), acrylates/C10-30alkyl acrylate crosspolymers, polyvinylpyrrolidone (PVP), polyvinylalcohol (PVA), and mixtures thereof, in a concentration of between about0.1%-10% w/w of the total composition, isopropanol or other short chainorganic alcohol in a concentration of between about 10%-30% w/w of thetotal composition, and a component selected from a group consisting of anon-aqueous co-solvent, a surfactant, and mixtures thereof as theremainder of the composition, wherein said pediculicidal and ovicidalcomposition is substantially free of acid.
 2. The composition of claim1, wherein the short chain alcohol is isopropanol.
 3. The composition ofclaim 2, wherein the isopropanol is in a concentration of about 20% w/wof the total composition.
 4. The composition of claim 1, wherein theisopropanol or other short chain alcohol is in a concentration ofbetween about 15%-25% w/w of the total composition.
 5. The compositionof claim 1, wherein the citronellyl acetate is in an at least 75% pureform.
 6. The composition of claim 1, wherein the citronellyl acetate isin a concentration of between 5%-15% w/w of the total composition. 7.The composition of claim 1, wherein the citronellyl acetate is in aconcentration of about 7.5-12.5% w/w of the total composition.
 8. Thecomposition of claim 1, wherein the citronellyl acetate is in aconcentration of about 10% w/w of the total composition.
 9. Thecomposition of claim 1, wherein the viscosity modifier is hydroxypropylmethylcelluose.
 10. The composition of claim 1, wherein the viscositymodifier is in a concentration of between about 0.25%-3% w/w of thetotal composition.
 11. The composition of claim 1 wherein the viscositymodifier is used in conjunction with a neutralizing agent.
 12. Thecomposition of claim 1, wherein the non-aqueous co-solvent is selectedfrom the group consisting of propylene glycol, butylene glycol,polyethylene glycol, hexylene glycol, methoxypolyethylene glycol,glycerin, and combinations thereof.
 13. The composition of claim 1,wherein the surfactant is sodium laureth sulfate, sodium lauryl sulfate,polysorbate or combination thereof.
 14. The composition of claim 1,wherein the surfactant is polyoxyethylene sorbitan monolaurate orpolysorbate.
 15. The composition of claim 1, wherein said pediculicidaland ovicidal composition further includes a component selected from thegroup consisting of an antioxidant/free radical scavenger, a pHmodifier, an antimicrobial agent, a chelating agent, a fragrance, afoaming agent, a conditioning agent, and combinations thereof.
 16. Thecomposition of claim 15, wherein said antimicrobial agent ispropylparaben.
 17. The composition of claim 15, wherein saidantimicrobial agent is methylparaben.
 18. The composition of claim 15,wherein said fragrance is methyl salicyclate.